CD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death

Merendino, Anna M; Bucchieri, Fabio; Gagliardo, Rosalia; Daryadel, Arezoo; Pompeo, Flora; Chiappara, Giuseppina; Santagata, Roberta; Bellia, Vincenzo; David, Sabrina; Farina, Felicia; Davies, Donna E; Simon, Hans-Uwe; Vignola, Antonio M (2006). CD40 ligation protects bronchial epithelium against oxidant-induced caspase-independent cell death. American journal of respiratory cell and molecular biology, 35(2), pp. 155-64. New York, N.Y.: American Lung Association 10.1165/rcmb.2005-0433OC

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CD40 and its ligand regulate pleiotropic biological responses, including cell proliferation, differentiation, and apoptosis. In many inflammatory lung diseases, tissue damage by environmental or endogenous oxidants plays a major role in disease pathogenesis. As the epithelial barrier is a major target for these oxidants, we postulated that CD40, the expression of which is increased in asthma, plays a role in the regulation of apoptosis of bronchial epithelial cells exposed to oxidants. Using 16HBE 14o- cells exposed to oxidant stress, we found that ligation of CD40 (induced by G28-5 monoclonal antibodies) enhanced cell survival and increased the number of cells in G2/M (interphase between DNA synthesis and mitosis) of the cell cycle. This was associated with NF-kappaB and activator protein-1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress-induced apoptosis was found to be caspase- and calpain-independent implicating CD40 ligation as a regulator of caspase-independent cell death. This was confirmed by the demonstration that CD40 ligation prevented mitochondrial release and nuclear translocation of apoptosis inducing factor. In conclusion, we demonstrate a novel role for CD40 as a regulator of epithelial cell survival against oxidant stress. Furthermore, we have identified, for the first time, an endogenous inhibitory pathway of caspase-independent cell death.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Simon, Hans-Uwe

ISSN:

1044-1549

ISBN:

16543604

Publisher:

American Lung Association

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:48

Last Modified:

17 Mar 2015 21:49

Publisher DOI:

10.1165/rcmb.2005-0433OC

PubMed ID:

16543604

Web of Science ID:

000239537500003

URI:

https://boris.unibe.ch/id/eprint/20236 (FactScience: 3423)

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